State-of-the-Art Automated Patch Clamp: Heat Activation, Action Potentials, and High Throughput in Ion Channel Screening

  • Sonja Stoelzle-FeixEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1183)


A successful robotic approach of the patch clamp technique is based on planar patch clamp chips where a glass pipette, as used in conventional patch clamping, is replaced by a thin planar glass sheet with a small hole in the middle. Automated patch clamp (APC) systems utilizing this chip design offer higher throughput capabilities and ease of use and thus have become common in basic research, drug development, and safety screening. Further development of existing devices and introduction of new systems widen the range of possible experiments and increase throughput. Here, two features with different areas of applications that meet the needs of drug discovery researchers and basic researchers alike are described. The utilized system is a medium throughput APC device capable of recording up to eight cells simultaneously. The temperature control capability and the possibility to perform recordings not only in the voltage clamp but also in the current clamp mode are described in detail. Since eight recordings can be generated in parallel without compromising data quality, reliable and cost-effective and time-effective screening of compounds against ion channels using voltage clamp and current clamp electrophysiology can be performed.

Key words

Automated patch clamp Action potential Current clamp Stem cell-derived cardiomyocytes High throughput Ion channel screening 


  1. 1.
    Neher E, Sakmann B (1976) Single channel currents recorded from membrane of denervated frog muscle fibres. Nature 260:799–802PubMedCrossRefGoogle Scholar
  2. 2.
    Dunlop J, Bowlby M, Peri R et al (2008) High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology. Nat Rev 7:358–368Google Scholar
  3. 3.
    Farre C, Haythornthwaite A, Haarmann C et al (2009) Port-a-patch and patchliner: high fidelity electrophysiology for secondary screening and safety pharmacology. Comb Chem High Throughput Screen 12:24–37PubMedCrossRefGoogle Scholar
  4. 4.
    Stoelzle S, Obergrussberger A, Brüggemann A et al (2011) State-of-the art automated patch-clamp devices: heat activation, action potentials, and high throughput in ion channel screening. Front Pharmacol 2:1–11CrossRefGoogle Scholar
  5. 5.
    Polonchuk L (2009) Toward a new gold standard for early safety: automated temperature-controlled hERG test on the Patchliner®. Front Pharmacol 3:3Google Scholar
  6. 6.
    Milligan CJ, Li J, Sukumar P, Majeed Y et al (2009) Robotic multiwell planar patch-clamp for native and primary mammalian cells. Nat Protoc 4:244–255PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Balansa W, Islam R, Fontaine F et al (2010) Ircinialactams: subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae. Bioorg Med Chem 18:2912–2919PubMedCrossRefGoogle Scholar
  8. 8.
    Stoelzle S, Haythornthwaite A, Kettenhofen R et al (2011) Automated patch-clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction. J Biomol Screen 16:910–916PubMedCrossRefGoogle Scholar
  9. 9.
    Farre C, Stoelzle S, Haarman C et al (2007) Automated ion channel screening: patch-clamping made easy. Expert Opin Ther Targets 11:557–565PubMedCrossRefGoogle Scholar
  10. 10.
    Brüggemann A, Farre C, Haarmann C, Haythornthwaite A et al (2008) Planar patch-clamp: advances in electrophysiology. Methods Mol Biol 491:165–176PubMedCrossRefGoogle Scholar
  11. 11.
    Majeed Y, Bahnasi Y, Seymour V et al (2010) Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. Mol Pharmacol 79:1023–1030CrossRefGoogle Scholar
  12. 12.
    Peier A, Reeve AJ, Andersson DA et al (2002) A heat-sensitive TRP channel expressed in keratinocytes. Science 296:2046–2049PubMedCrossRefGoogle Scholar
  13. 13.
    Xu H, Ramsey IS, Kotecha SA et al (2002) TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418:181–186PubMedCrossRefGoogle Scholar
  14. 14.
    Smith GD, Gunthorpe MJ, Kelsell RE et al (2002) TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418:186–190PubMedCrossRefGoogle Scholar
  15. 15.
    Chung MK, Lee H, Mizuno A et al (2004) 2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3. J Neurosci 24:5177–5182PubMedCrossRefGoogle Scholar
  16. 16.
    Kolossov E, Bostani T, Roell W et al (2006) Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile Function to the infarcted myocardium. J Exp Med 203:2315–2327PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Hu H, Grandl J, Bandell M et al (2009) Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4. Proc Natl Acad Sci U S A 106:1626–1631PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Becker N, Stoelzle S, Göpel S et al (2013) Minimized cell usage for stem cell-derived and primary cells on an automated patchclamp system. J Pharmacol Toxicol Meth 68(1):82–87, pii: S1056-8719(13)00232-3CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Nanion Technologies GmbHMunichGermany

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